Bottom Line:
Our results showed that inhibition of iNOS by SMT could make different response in male and female animals.It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male.However, such beneficial effect was not observed in female animals.

Backgrounds: It has been previously demonstrated that the increase of nitric oxide (NO) level may promote cisplatin (CP)-induced nephrotoxicity. The aim of this study was to investigate the role of inducible NO synthase (iNOS) inhibitor to prevent CP-induced nephrotoxicity.

Materials and methods: Four groups of male and four groups of female rats were treated daily with vehicle, S-methylisothiourea hemisulfate (SMT) as a selective iNOS inhibitor (5 mg/kg/twice a day), CP (2.5 mg/kg/day), and CP + SMT for 6 days. Then, all animals were sacrificed and the serum levels of creatinine (Cr), blood urea nitrogen (BUN), nitrite, and malondialdehyde (MDA) were measured. The kidney was removed immediately for histopathological study.

Results: Our results showed that inhibition of iNOS by SMT could make different response in male and female animals. SMT therapy in male animals decreased serum BUN, Cr, nitrite, and MDA levels; and it also protected kidney against CP-induced nephrotoxicity.

Conclusion: It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male. However, such beneficial effect was not observed in female animals.

Figure 2: The images of kidney tissue in male and female rats treated with saline, CP, SMT, and combination of SMT and CP (SMT+CP)

Mentions:
The CP-induced kidney damage was evaluated and scored by a pathologist. Significantly higher kidney damage scores were obtained in the CP-treated groups when compared with the sham group in both males and females (P < 0.05). Although therapy with SMT alone did not have any deleterious effects on kidney tubular structures, its combination with CP decreased kidney tissue damage score (KTDS) insignificantly in male. The images of kidney tissue in all groups are illustrated in Figure 2.

Figure 2: The images of kidney tissue in male and female rats treated with saline, CP, SMT, and combination of SMT and CP (SMT+CP)

Mentions:
The CP-induced kidney damage was evaluated and scored by a pathologist. Significantly higher kidney damage scores were obtained in the CP-treated groups when compared with the sham group in both males and females (P < 0.05). Although therapy with SMT alone did not have any deleterious effects on kidney tubular structures, its combination with CP decreased kidney tissue damage score (KTDS) insignificantly in male. The images of kidney tissue in all groups are illustrated in Figure 2.

Bottom Line:
Our results showed that inhibition of iNOS by SMT could make different response in male and female animals.It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male.However, such beneficial effect was not observed in female animals.

Backgrounds: It has been previously demonstrated that the increase of nitric oxide (NO) level may promote cisplatin (CP)-induced nephrotoxicity. The aim of this study was to investigate the role of inducible NO synthase (iNOS) inhibitor to prevent CP-induced nephrotoxicity.

Materials and methods: Four groups of male and four groups of female rats were treated daily with vehicle, S-methylisothiourea hemisulfate (SMT) as a selective iNOS inhibitor (5 mg/kg/twice a day), CP (2.5 mg/kg/day), and CP + SMT for 6 days. Then, all animals were sacrificed and the serum levels of creatinine (Cr), blood urea nitrogen (BUN), nitrite, and malondialdehyde (MDA) were measured. The kidney was removed immediately for histopathological study.

Results: Our results showed that inhibition of iNOS by SMT could make different response in male and female animals. SMT therapy in male animals decreased serum BUN, Cr, nitrite, and MDA levels; and it also protected kidney against CP-induced nephrotoxicity.

Conclusion: It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male. However, such beneficial effect was not observed in female animals.